人类乳腺癌基因表达分析

目的研究乳腺癌发生和发展相关基因群的表达及其初步功能。方法用4096种人类基因多聚酶链反应(PcR)产物制成BioDoor4096型表达谱芯片，分离纯化正常乳腺组织和乳腺癌组织mRNA，制备表达谱探针，用ScanArray3000荧光扫描仪扫描芯片荧光信号图像，利用计算机分析正常乳腺组织和乳腺癌组织之间差异表达的基因。结果在4096种基因中，正常乳腺组织和乳腺癌组织之间差异表达的基因有619条(15．11％)。生物信息学分析显示，这些差异表达的基因可能与乳腺癌的发生和发展密切相关。结论乳腺癌的发生、发展中存在多基因表达调控的改变，对于相关基因群的研究有助于认识肿瘤发病机制，并为乳腺癌个体化治疗提供依据。     

miRNA与乳腺癌转移

肿瘤转移是造成乳腺癌患者死亡的主要原因.最新研究表明,一些miRNA在转录后水平调控乳腺癌转移相关基因的表达,与乳腺癌的侵袭和转移密切相关.本文针对参与调控乳腺癌侵袭和转移的miRNA及其作用机制做以综述.     

FOXA1通过调控XBP1的转录促进乳腺癌增殖的功能及机制研究

目的 探究先锋转录因子FOXA1在乳腺癌中的功能及其发挥功能的分子机制。方法利用cBioPortal数据库分析FOXA1在肿瘤中的突变情况,利用TCGA数据库分析FOXA1在乳腺癌组织中的mRNA表达水平及其与患者预后的关系;采用CCK-8和克隆集落形成实验探究FOXA1和X盒结合蛋白1(XBP1)对ERα阳性乳腺癌细胞增殖能力的影响;采用流式细胞技术分析FOXA1对ERα阳性乳腺癌细胞周期的影响;联合转录组学和GEO数据库分析乳腺癌中受FOXA1调控的基因及信号通路;采用蛋白质印迹技术和RT-qPCR技术验证受FOXA1调控的基因的表达情况。结果 在肿瘤中,FOXA1在多个位点发生突变;FOXA1在乳腺癌组织中的表达水平显著高于正常组织,并且FOXA1的高表达与患者的不良预后呈正相关;相比于其他乳腺癌分型,FOXA1在Luminal型乳腺癌中呈显著高表达;转录组和染色质免疫共沉淀分析一共鉴定到177个受FOXA1直接转录调控的基因,其中包括XBP1;通路富集分析表明,受FOXA1调控的基因显著富集在细胞周期和DNA复制通路上;在ERα阳性乳腺癌细胞系中,沉默FOXA1或者XBP1的表...     

苦参碱对乳腺癌细胞bcl-2蛋白、bax蛋白、Fas抗原表达水平的影响

近年研究表明，多数抗乳腺癌的化疗药物诱导细胞凋亡的作用机制与多种基因的调控有关，细胞凋亡的发生是一个有多种相关基因相互作用的复杂事件。有研究证实从西北中药苦豆子中提取的苦参碱可抑制人乳腺癌细胞的生长并诱导凋亡。我们通过苦参碱诱导人乳腺癌细胞MCF-7／ADR凋亡，检测与凋亡有关基因bcl-2、bax、Fas表达的变化，探讨苦参碱诱导肿瘤细胞凋亡的分子作用机制。[第一段]     

Sox基因的异常表达与乳腺癌研究的进展

Sox基因家族是一类SRY相关基因构成的基因家族,编码一系列Sox家族的转录因子.Sox基因在个体发育过程中参与了性别决定和分化、神经发育、软骨形成等多种发育过程.近年研究者发现,Sox基因的异常表达与乳腺癌的发生、发展有一定关系,如Sox2、Sox4的过表达与乳腺癌的发生相关;Sox7和Sox17在乳腺癌中可作为抑癌基因,其表达下调可激活Wnt/β-catenin信号通路,与乳腺癌的发生发展有一定关系.     

实时PCR检测Her-2扩增状态对乳腺癌新辅助化疗治疗机理的初探

目的：检测Her-2基因拷贝量在新辅助化疗（NAC）前后的表达情况，初步探讨化疗药物对预后因子表达的调控。
方法：采用实时PCR方法检测28例乳腺癌初治患者在接受新辅助化疗后，乳腺癌组织中Her-2基因拷贝量的变化情况。
结果：新辅助化疗前Her-2基因拷贝量明显高于化疗后，但其Her-2基因拷贝量的改变与病例临床分期和化疗周期数目无关。
结论：新辅助化疗能使乳腺癌Her-2基因拷贝量减少，下调Her-2基因的表达，提示新辅助化疗也可能通过下调Her-2基因的表达，而改善乳腺癌患者的预后。

     

CyclinD_1基因扩增及其蛋白表达在乳腺癌中的意义

目的　探讨乳腺癌中CyclinD1基因扩增和其蛋白表达的相关性及其临床意义。方法　应用半定量PCR和免疫组化技术 ,检测和分析了乳腺癌及其癌旁组织、乳腺良性组织及正常乳腺标本中CyclinD1基因的扩增和CyclinD1蛋白的表达情况。结果　 62例乳腺癌中 ,CyclinD1基因扩增占 2 2 .6% ( 14 /62 ) ,蛋白过度表达占 48.4% ( 3 0 /62 ) ,二者有一定相关性 ,而其它各种乳腺组织的CyclinD1基因扩增及蛋白过度表达与之相比差异有显著性意义 (P <0 .0 5 )。Cy clinD1基因扩增及蛋白过度表达与乳腺癌组织学分级呈明显正相关 ,且CyclinD1蛋白过度表达还与雌孕激素受体状况呈正相关。结论　乳腺癌中CyclinD1基因扩增程度和其蛋白过度表达虽有一定相关性 ,但并不完全一致 ,说明还存在着其它导致CyclinD1蛋白过度表达的机理 ,CyclinD1蛋白的表达可能还受雌激素的调控。对乳腺癌中CyclinD1基因及其蛋白表达的检测有一定临床意义。     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

瘦素在乳腺癌发病中的作用

瘦素是一种由肥胖基因(ob基因)编码表达的小分子蛋白,在调控机体的摄食行为和脂肪代谢方面具有重要作用.近来大量研究发现瘦素在体外可促进乳腺细胞转化、癌细胞增生并促进血管生成.这表明瘦素在乳腺癌的发生发展中可能起重要作用,但具体机制尚未阐明.本文主要从体外实验、动物试验和乳腺癌病理组织研究3方面对瘦素在乳腺癌发病中的作用的近年相关研究进展进行综述.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Development of Selective Low-Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL-Specific Adsorption for LDL Apheresis System

Abstract: Low-density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL-lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im-munoadsorbent utilizing an anti-LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL-removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion-rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 10⁴ daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high-density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL-binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow-fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.     

Artificial organs 2010: a year in review

In this Editor's Review, articles published in 2010 are organized by category and briefly summarized. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, and the International Society for Rotary Blood Pumps, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level."Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide such meaningful suggestions to the author's work whether eventually accepted or rejected and especially to those whose native tongue is not English. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, Wiley-Blackwell, for their expert attention and support in the production and marketing of Artificial Organs. In this Editor's Review, that historically has been widely received by our readership, we aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. We look forward to recording further advances in the coming years.     

Avaliação do clube de revista de anestesiologia por meio de mudanças semânticas

Background and objectives

The interactive approach of a journal club has been described in the medical education literature. The aim of this investigation is to present an assessment of journal club as a tool to address the question whether residents read more and critically.

Methods

This study reports the performance of medical residents in anesthesiology from the Clinics Hospital – University of São Paulo Medical School. All medical residents were invited to answer five questions derived from discussed papers. The answer sheet consisted of an affirmative statement with a Likert type scale (totally disagree–disagree–not sure–agree–totally agree), each related to one of the chosen articles. The results were evaluated by means of item analysis – difficulty index and discrimination power.

Results

Residents filled one hundred and seventy three evaluations in the months of December 2011 (n = 51), July 2012 (n = 66) and December 2012 (n = 56). The first exam presented all items with straight statement, second and third exams presented mixed items. Separating “totally agree” from “agree” increased the difficulty indices, but did not improve the discrimination power.

Conclusions

The use of a journal club assessment with straight and inverted statements and by means of five points scale for agreement has been shown to increase its item difficulty and discrimination power. This may reflect involvement either with the reading or the discussion during the journal meeting.     

Lymphocytapheresis

Abstract: Leukocytapheresis has long been performed with the centrifugal method. But in 1989 in Japan, the Asahi Medical Co. developed the extracorporeal leukocyte-removal filter, Cellsorba. This filter consists of non-woven fabric, which can remove leukocytes from whole blood during extracorporeal circulation. In the incipient stage, this filter was applied to collagen diseases, rheumatoid arthritis, and systemic lupus erythematosus. During the following studies, this filter has been found to have an immunosuppressive effect. Now, it is beginning to be applied to various kinds of autoimmune diseases. Moreover, this filter has recently been recognized to be effective in inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. The outline of Cellsorba and the application of this filter is described here.     

Soluble TNFα Receptors Are Increased in Chronic Renal Insufficiency and Hemodialysis and Inhibit Neutrophil Priming by TNFα

Abstract: The oxidative burst of neutrophils from azotemic patients is refractory to priming by tumor necrosis factor-α (TNFα). Soluble TNFα binding proteins (TNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNFa priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNFa priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sTNFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNFα primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNFα in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNFα priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.